The need for detection of biological agents in a variety of applications is acute. The rapid detection of very small quantities of harmful molecules, DNA, viruses, etc. using inexpensive, disposable sensors is particularly important.
A number of methods have been developed that allow such detection. Microelectromechanical (MEMS) technology plays a major role in this field because MEMS sensors can be batch-processed for low cost and are capable of handling and detecting very small quantities of unknown substances. Small amounts of materials, often in the range of pico or femto liters, can be handled and measured.
Nanoresonators and microresonators are resonators that have linear dimensions on the order of nanometers and micrometers, respectively. Such silicon-based nanoresonators may have resonant frequencies as high as 600 MHz and a quality factor Q in the range of 1000-2000. Kubena et al (U.S. patent application Ser. No. 10/426,931) disclose a method for fabricating and integrating quartz-based nanoresonators on a high speed substrate for integrated signal processing by utilizing a combination of novel bonding and etching steps to form ultra thin quartz-based resonators with a resonant frequency in excess of 100 MHz.
Raman spectroscopy is commonly used to identify functional groups in a molecule. Surface enhanced Raman spectroscopy (SERS) provides enhanced detection capability permitting picomolar detection levels of chemical and biological species. In general, Raman spectroscopy provides real time detection of molecules in a non-contact mode, thereby avoiding sample contamination. Natan (U.S. Pat. No. 6,514,767 and U.S. Ser. No. 11/132,471) disclose a method for increasing the sensitivity of SERS for detection of known species with metal nanoparticle “tags” (nanotags).
For the detection of biological molecules, sensors in the prior art that may be sufficiently selective are not sensitive enough to monitor the presence of picomolar or nanomolar levels of a given molecule. On the other hand, highly sensitive sensors are not selective enough to discriminate at the molecular level, which is needed to differentiate various strains of bacteria. Therefore, a need continues to exist for small, easy to use sensors that offer high selectivity, high sensitivity, and sufficient accuracy for the monitoring of biological species.